A liposomal composition (“ADx-003”) is provided, ADx-003 comprising a first phospholipid; a sterically bulky excipient that is capable of stabilizing the liposomal composition; a second phospholipid that is derivatized with a first polymer; a macrocyclic gadolinium-based imaging agent; and a third phospholipid that is derivatized with a second polymer, the second polymer being conjugated to a targeting ligand, the targeting ligand being represented by Formula I: ##STR00001##
wherein X is —CH.sub.2—, —CH.sub.2—CH.sub.2—, —CHO—, or —O—CO—; Y is —CH—CH═CH— or ##STR00002##
A and B are independently selected from C and N; R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are independently selected from —H, halogen, —OH, and —CH.sub.3; and R.sub.5, R.sub.6, and R.sub.7 are independently selected from —H, halogen, —OH, —OCH.sub.3, —NO.sub.2, —N(CH.sub.3).sub.2, C.sub.1-C.sub.6 alkyl, or a substituted or unsubstituted C.sub.4-C.sub.6 aryl group, except that when A and/or B is N the adjacent R.sub.5 and/or R.sub.7 is —H, or a pharmaceutically acceptable salt thereof.

A liposomal composition (“ADx-003”) is provided, ADx-003 comprising a first phospholipid; a sterically bulky excipient that is capable of stabilizing the liposomal composition; a second phospholipid that is derivatized with a first polymer; a macrocyclic gadolinium-based imaging agent; and a third phospholipid that is derivatized with a second polymer, the second polymer being conjugated to a targeting ligand, the targeting ligand being represented by Formula I: ##STR00001##
wherein X is —CH.sub.2—, —CH.sub.2—CH.sub.2—, —CHO—, or —O—CO—; Y is —CH—CH═CH— or ##STR00002##
A and B are independently selected from C and N; R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are independently selected from —H, halogen, —OH, and —CH.sub.3; and R.sub.5, R.sub.6, and R.sub.7 are independently selected from —H, halogen, —OH, —OCH.sub.3, —NO.sub.2, —N(CH.sub.3).sub.2, C.sub.1-C.sub.6 alkyl, or a substituted or unsubstituted C.sub.4-C.sub.6 aryl group, except that when A and/or B is N the adjacent R.sub.5 and/or R.sub.7 is —H, or a pharmaceutically acceptable salt thereof.

A liposomal composition (“ADx-003”) is provided, ADx-003 comprising a first phospholipid; a sterically bulky excipient that is capable of stabilizing the liposomal composition; a second phospholipid that is derivatized with a first polymer; a macrocyclic gadolinium-based imaging agent; and a third phospholipid that is derivatized with a second polymer, the second polymer being conjugated to a targeting ligand, the targeting ligand being represented by Formula I:

##STR00001##

wherein X is —CH.sub.2—, —CH.sub.2—CH.sub.2—, —CHO—, or —O—CO—; Y is —CH—CH═CH— or

##STR00002##

A and B are independently selected from C and N; R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are independently selected from —H, halogen, —OH, and —CH.sub.3; and R.sub.5, R.sub.6, and R.sub.7 are independently selected from —H, halogen, —OH, —OCH.sub.3, —NO.sub.2, —N(CH.sub.3).sub.2, C.sub.1-C.sub.6 alkyl, or a substituted or unsubstituted C.sub.4-C.sub.6 aryl group, except that when A and/or B is N the adjacent R.sub.5 and/or R.sub.7 is —H, or a pharmaceutically acceptable salt thereof.

A liposomal composition (“ADx-003”) is provided, ADx-003 comprising a first phospholipid; a sterically bulky excipient that is capable of stabilizing the liposomal composition; a second phospholipid that is derivatized with a first polymer; a macrocyclic gadolinium-based imaging agent; and a third phospholipid that is derivatized with a second polymer, the second polymer being conjugated to a targeting ligand, the targeting ligand being represented by Formula I:

##STR00001##

wherein X is —CH.sub.2—, —CH.sub.2—CH.sub.2—, —CHO—, or —O—CO—; Y is —CH—CH═CH— or

##STR00002##

A and B are independently selected from C and N; R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are independently selected from —H, halogen, —OH, and —CH.sub.3; and R.sub.5, R.sub.6, and R.sub.7 are independently selected from —H, halogen, —OH, —OCH.sub.3, —NO.sub.2, —N(CH.sub.3).sub.2, C.sub.1-C.sub.6 alkyl, or a substituted or unsubstituted C.sub.4-C.sub.6 aryl group, except that when A and/or B is N the adjacent R.sub.5 and/or R.sub.7 is —H, or a pharmaceutically acceptable salt thereof.

Disclosed are compounds that can modulate DDAH and the amount of asymmetric dimethylarginine (ADMA) in a subject. Also provided are pharmaceutical compositions comprising these compounds, as well as methods of using these compositions to treat and/or prevent diseases associated with elevated or low levels of DDAH and ADMA.

Disclosed are compounds that can modulate DDAH and the amount of asymmetric dimethylarginine (ADMA) in a subject. Also provided are pharmaceutical compositions comprising these compounds, as well as methods of using these compositions to treat and/or prevent diseases associated with elevated or low levels of DDAH and ADMA.

The present disclosure provides a benzene fused heterocyclic derivative of Formula (I): is a single or double bond; n is an integer of 0 or 1; A is —CH.sub.2—, —CH(OH)—, or —C(O)—; G is C or N; X is —CH.sub.2—, O, or —C(O)—; Y is alkyl, aryl, or heterocyclic alkyl optionally substituted with at least one substituent independently selected from a group consisting of: H, halogen, alkyl, alkyl substituted with at least one halogen, aryl, aryl substituted with at least one halogen, —NR.sub.y1R.sub.y2, —OR.sub.y1, —R.sub.y1C(O)R.sub.y3, —C(O)R.sub.y1, —C(O)OR.sub.y2, —C(O)OR.sub.y2Ry3, —NR.sub.y1C(O)R.sub.y2, —NR.sub.y1C(O)NR.sub.y2R.sub.y3, —NR.sub.y1C(O)OR.sub.y2R.sub.y3, —NR.sub.y1C(O)R.sub.y2OR.sub.y3, C(O)NR.sub.y1(R.sub.y2R.sub.y3), —C(O)NR.sub.y1(R.sub.y2OR.sub.y1), —OR.sub.y2R.sub.y3, and —OR.sub.y2OR.sub.y3, wherein each of R.sub.y1 and R.sub.y2 is independently selected from a group consisting of H, oxygen, alkyl, and aryl, and R.sub.y3 is aryl optionally substituted with at least one halogen; Z is —NR.sub.z1R.sub.z2, —NR.sub.z1R.sub.z3, —OR.sub.z1, —OR.sub.z1R.sub.z3, —C(O)R.sub.z1R.sub.z3, —C(O)OR.sub.z1R.sub.z3, —NR.sub.z1C(O)R.sub.z2R.sub.z3, —NR.sub.z1C(O)OR.sub.z2R.sub.z3, —C(O)NR.sub.z1R.sub.z3, or OR.sub.z2OR.sub.z3, wherein each of R.sub.z1 and R.sub.z2 is independently selected from a group consisting of H, oxygen, alkyl and aryl, and R.sub.z3 is aryl optionally substituted with at least one substituent independently selected from a group consisting of halogen, OH, —R.sub.zaCOOR.sub.zb, —OR.sub.zaCOOR.sub.zb, —R.sub.zaSO.sub.2R.sub.zb, —R.sub.zaSO.sub.2NR.sub.zbR.sub.zcR.sub.zd, —R.sub.zaC(O)R.sub.zbR.sub.zc, —R.sub.zaC(O)NR.sub.zbR.sub.zcR.sub.zd, —RZ.sub.aC(O)NR.sub.zbSO.sub.2R.sub.zc, wherein Rza is nil or alkyl, R.sub.zb is H or alkyl, each of R.sub.zb and R.sub.zc is independently selected from a group consisting of H, OH, alkyl, aryl, alkoxyl, or NR.sub.zbR.sub.zc is a nitrogen-containing heterocyclic alkyl ring, R.sub.zd is nil or a sulfonyl alkyl group. ##STR00001##

A liposomal composition (“ADx-003”) is provided, ADx-003 comprising a first phospholipid; a sterically bulky excipient that is capable of stabilizing the liposomal composition; a second phospholipid that is derivatized with a first polymer; a macrocyclic gadolinium-based imaging agent; and a third phospholipid that is derivatized with a second polymer, the second polymer being conjugated to a targeting ligand, the targeting ligand being represented by Formula I:

##STR00001##

wherein X is —CH.sub.2—, —CH.sub.2—CH.sub.2—, —CHO—, or —O—CO—; Y is —CH—CH═CH— or

##STR00002##

A and B are independently selected from C and N; R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are independently selected from —H, halogen, —OH, and —CH.sub.3; and R.sub.5, R.sub.6, and R.sub.7 are independently selected from —H, halogen, —OH, —OCH.sub.3, —NO.sub.2, —N(CH.sub.3).sub.2, C.sub.1-C.sub.6 alkyl, or a substituted or unsubstituted C.sub.4-C.sub.6 aryl group, except that when A and/or B is N the adjacent R.sub.5 and/or R.sub.7 is —H, or a pharmaceutically acceptable salt thereof.

A liposomal composition (“ADx-003”) is provided, ADx-003 comprising a first phospholipid; a sterically bulky excipient that is capable of stabilizing the liposomal composition; a second phospholipid that is derivatized with a first polymer; a macrocyclic gadolinium-based imaging agent; and a third phospholipid that is derivatized with a second polymer, the second polymer being conjugated to a targeting ligand, the targeting ligand being represented by Formula I:

##STR00001##

wherein X is —CH.sub.2—, —CH.sub.2—CH.sub.2—, —CHO—, or —O—CO—; Y is —CH—CH═CH— or

##STR00002##

A and B are independently selected from C and N; R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are independently selected from —H, halogen, —OH, and —CH.sub.3; and R.sub.5, R.sub.6, and R.sub.7 are independently selected from —H, halogen, —OH, —OCH.sub.3, —NO.sub.2, —N(CH.sub.3).sub.2, C.sub.1-C.sub.6 alkyl, or a substituted or unsubstituted C.sub.4-C.sub.6 aryl group, except that when A and/or B is N the adjacent R.sub.5 and/or R.sub.7 is —H, or a pharmaceutically acceptable salt thereof.

A liposomal composition (“ADx-003”) is provided, ADx-003 comprising a first phospholipid; a sterically bulky excipient that is capable of stabilizing the liposomal composition; a second phospholipid that is derivatized with a first polymer; a macrocyclic gadolinium-based imaging agent; and a third phospholipid that is derivatized with a second polymer, the second polymer being conjugated to a targeting ligand, the targeting ligand being represented by Formula I:

##STR00001##

wherein X is —CH.sub.2—, —CH.sub.2—CH.sub.2—, —CHO—, or —O—CO—; Y is —CH—CH═CH— or

##STR00002##

A and B are independently selected from C and N; R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are independently selected from —H, halogen, —OH, and —CH.sub.3; and R.sub.5, R.sub.6, and R.sub.7 are independently selected from —H, halogen, —OH, —OCH.sub.3, —NO.sub.2, —N(CH.sub.3).sub.2, C.sub.1-C.sub.6 alkyl, or a substituted or unsubstituted C.sub.4-C.sub.6 aryl group, except that when A and/or B is N the adjacent R.sub.5 and/or R.sub.7 is —H, or a pharmaceutically acceptable salt thereof.